Endocrine Flashcards
Carbimazole
- Thionamide (antithyroid drug)
- drug of choice
- prodrug; converted to the active metabolite thiamazole via first pass metabolism
- has immunosuppressive properties and thus is useful in the treatment of Graves’ disease
- some serious side effects (agranulocytosis, skin aplasia, rash, nausea, vomiting)
propiothiouracil (PTU)
- Thionamide (antithyroid drug)
- Less active and shorter half life than carbimazole so twice the dosing is required.
- PTU usually second line.
- reduces the conversion of T4 → T3 peripherally giving some more acute effects.
- better safety data in pregnancy
Propanolol
- beta blocker
- used for symptomatic treatment in hyperthyroidism
- do not affect hormone levels
Potassium Iodide
- antithyroid drug
- Reduces thyroid hormone release acutely, used in thyroid storm and pre-operatively
levothyroxine
- synthetitc T4 used to treat hypothyroidism
- Generally need 1.7-2.0 micrograms / kg / day (with no gland whatsoever)
- Best taken on an empty stomach
- Avoid taking with proton pump inhibitors, ferrous sulphate or calcium
- Start lower, especially in elderly and in cardiac disease
- Increased thyroxine increases the load on the heart
Cabergoline
- Dopamine agonist (D2 receptor agonist)
- treatment of prolactinoma
- Most commonly used, well tolerated
- Long half-life, therefore only requires once/twice weekly dosing
- Also used to treat parkinson’s (but higher doses)
- Association with cardiac fibrosis
- Echocardiogram at the start of treatment to determine if there is any fibrosis
Quinagolide
- Dopamine agonist
- treatment of prolactinoma
Bromocriptine
- Dopamine agonist
- treatment of prolactinoma
Thionamides
Reduce thyroid hormone synthesis
o Inhibit iodide oxidation
o Inhibit iodination of tyrosine
o Inhibit coupling of iodotyrosines
- T4 has a long half-life (7 days) and therefore treatment with antithyroid drugs can take from 10-20 days for any clinical benefit to be seen.
Hydrocortisone
- cortisol replacement therapy
- used in adrenal insufficiency
- treatment is initially empirical, as waiting could be fatal
- Metabolised to cortisol. Most physiological way of replacing cortisol
- If unwell, give intravenously first
- Then 15-30mg oral tablets daily in divided doses (for long-term maintenance)
- Try to mimic diurnal rhythm
- Highest levels in the morning, therefore give higher dose in the morning
patient education is important:
- ‘sick day rules’ – double oral hydrocortisone for 3 days when unwell
- Cannot stop suddenly, as this will cause adrenal crisis
- Need to wear identification
Fludrocortisone
- aldosterone replacement therapy for primary adrenal insufficiency
- not used for secondary insufficiency because aldosterone is regulated by RAAS, not the pituitary
- Careful monitoring of BP and plasma potassium to determine the adequacy of replacement
Metyrapone/ketoconazole
- Inhibit cortisol production, but not very well
tolerated - Short term measure for treating cortisol excess
spironolactone
- Competitive antagonist at MR, androgen and progesterone receptors
- Unwanted side effects gynaecomastia, hyperkalaemia
- Management of Primary Aldosteronism
eplerenone
- Selective MR antagonist, no observed anti-androgen effects
- Management of Primary Aldosteronism
amiloride
- blocks ENaC, therefore blocks effect of
aldosterone - Management of Primary Aldosteronism
PHAEOCHROMOCYTOMA pre-operative treatment
- α1 +/- β1 antagonists to block effects of catecholamine surge
- Can become haemodynamically unstable in surgery if this is not done
fludrocortisone
- aldosterone replacement therapy
- used for primary adrenal insufficiency
Hydrocortisone
- cortisol replacement therapy
- used for primary and secondary adrenal insufficiency
- Metabolised to cortisol. Most physiological way of replacing cortisol
- dosing aims to mimic diurnal rhythm
Tamsulosin
- alpha 1 antagonist
- causes relaxation of smooth muscle in BPH
Treatment of hypercalcaemia
1) bisphosphonates - inhibit osteoclasts
2) calcitonin - given as a SC injection, opposes the action of PTH but only effective for 48 hours
3) glucocorticoid therapy - inhibits vitamin D production
4) if primary hyperparathyroidism and resistant to treatment - parathyroidectomy
Biguanides
Metformin
Mimic action of insulin by suppressing hepatic gluconeogenesis.
Inhibits PEPCK and G6Pase
sulphonylureas
gliclazide, glipizide, glibenclamide
block ATP-dependent K+ channel, increasing insulin release
May predispose to hypoglycaemia
Associated with weight gain
Thiazolidinediones
pioglitazone
stimulate expression of genes involved in triglyceride
storage.
o PPARγ agonists
o increase transcription of insulin sensitising genes
Stop inappropriate deposition of lipid in non-adipose tissues (which leads to insulin resistance) – improves insulin sensitivity
Associated with weight gain
The incretin effect
Observation that more insulin is released when glucose is ingested orally as opposed to injected.
Dependent on incretins - gut hormones that sensitize beta cells to stimulate more insulin release
o Glucagon-like peptide-1 (GLP-1)
o Gastric inhibitory peptide (GIP)
Rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin mimetics
Exanatide, Liraglutide
o Mimic incretins (GLP-1)
o Engineered for slower breakdown - not cleaved by DPP-4
o Injected – improve endogenous insulin secretion
associated with weight loss
DPP-4 inhibitors
sitagliptin, Vildagliptin
o Inhibit DPP-4 - enzyme that breaks down endogenous incretins
o Increase endogenous incretin-mediated increase in insulin secretion
o Oral drugs
SGLT2 INHIBITORS
Canagliflozin, Dapagliflozin, Empagliflozin
Inhibit renal re-uptake of glucose from filtrate by SGLT2
Reduce hyperglycaemia by increased loss of glucose through urine
o NB: makes patients more prone to UTIs
Marked effect on weight loss (due to calorie loss) and blood pressure (due to osmotic diuresis)
No risk of hypoglycaemia
Which drugs increase insulin release?
1) sulphonylureas
2) incretin mimetics
3) DPP-4 inhibitors
Which drugs increase insulin sensitivity?
1) biguanides
2) thiazolidinediones
What are first line drugs for type 2 diabetes?
metformin or sulphonylurea
What are second line drugs for type 2 diabetes?
Metformin therapy and addition of:
sulphonylurea or DPP-4i or thiazolidinedione
acarbose
inhibits alpha glucosidase, an intestinal enzyme that releases glucose from larger carbohydrates.
Orlistat
works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine
Bisphosphonates
reduce bone resorption - inhibit osteoclast activity
alendronate
zolendronate
Denosumab
monoclonal antibody that inhibits RANK ligand which signals to osteoclasts, therefore reduces resorption
Teriparatide
recombinant parathyroid hormone, binds to osteoblasts to increase bone formation
Dexamethasone
glucocorticoid action only
hydrocortisone
1:1 glucocorticoid:mineralocorticoid action
most physiologically similar to cortisol
